MGP-4 version 5

Our ‘Flexible’ Targeted Therapies Panel – assessing Hotspots, Copy Number Gains and Gene Fusions

This is our  entirely bespoke Multi-Gene Panel (MGP), intended to help guide the use of targeted anti-cancer therapies in common solid tumours. Launched in mid-2020, following extensive validation and ISO15189 accreditation, we were able to replace all of our preceding panels (MGP-1,2 & 3) with this very robust, sensitive and highly informative solution. MGP-4 is also very cost effective, providing as much clinically actionable information as many larger and considerably more expensive panels.

It is available in a fully flexible format, with service users able to choose only the DNA component (for hot-spot variants & copy number gains- CNGs), only the RNA component (for gene fusions), or both DNA/RNA combined. With combined testing, both components can be requested ‘upfront’ to save time, or alternatively with an option to reflex to RNA analysis only if the DNA based analysis proves uninformative, thus saving money and potentially precious tissue.

MGP-4 combines the highest utility targets from our previous three panels and also allows formal* reporting of copy number gains (CNGs) in relevant genes and suitable samples. However, please note that relative tumour content requirements are higher for CNG reporting (>20%) than for hotpots (>5%).

*CNGs have previously been reported, but only as incidental findings, requiring appropriate confirmation before being used for clinical decision making.

SNVs, Small Indels & Copy Number Gains (MGP-4DNA)

SNV – A single nucleotide variant; Small Indel – An Insertion, deletion or substitution of between 1 and 50 nucleotides; Copy Number Gains (>4 fold in >20% tumour samples)  are detected via proprietary in house analysis pipeline and are indicative only.

Gene	RefSeq Transcript	Exons	Codons
AKT1	NM_001382430.1	4, 5, 12	17-50, 65-93, 322-373
ALK	NM_004304.3	22, 23, 24, 25	1151-1171, 1173-1214, 1216-1247, 1249-1275
BRAF	NM_004333.6	11, 12, 14, 15, 16	450-477, 479-494, 566-589, 582-611, 623-659
CCNE1	NM_001238.4	3, 4, 6, 7, 8, 11	12-37, 42-60, 110-137, 167-195, 204-235, 319-333
CDK4	NM_000075.4	2, 6	8-49, 212-224
CDK6	NM_001145306.2	5	180-215
CDKN2A	NM_000077.5	1, 2, 3	13-39, 51-88, 98-139, 154-157
CTNNB1	NM_001904.4	3	13-50
CXCR4	NM_003467.3	1	315-354
EGFR†	NM_005228.5	3, 7, 12, 15, 17, 18, 19, 20, 21	85-125, 282-296, 474-499, 583-625, 641-671, 696-725, 729-761, 762-799, 814-823, 827-865
ERBB2†	NM_004448.4	8, 12, 14, 16, 17 ,18 ,19, 20, 21, 22, 24, 25	302-326, 472-501, 557-579, 634-648, 650-679, 718-736, 737-760, 770-797, 832-870, 884-903, 969-990, 1007-1048
ESR1	NM_000125.4	3, 4, 5, 7, 8	233-253, 300-339, 367-384, 458-481, 533-574
FBXW7	NM_001349798.2	7, 10, 11, 12, 13	256-287, 379-402, 435-472, 479-508, 567-593
FGFR1	NM_023110.3	3, 4, 8, 10, 12, 14, 17	44-79, 121-147, 315-356, 439-476, 529-554, 640-659, 730-758
FGFR2	NM_000141.5	3, 5, 7, 9, 12, 14, 16	71-113, 179-204, 251-269, 284-313, 363-395, 527-557, 647-662, 715-731
FGFR3	NM_000142.5	7, 9, 13, 15, 16	248-260, 369-412, 559-590, 654-662, 690-721
GNA11	NM_002067.4	4, 5	166-196, 206-240
GNAQ	NM_002072.5	2, 4, 5	60-99, 164-201, 203-223
GNAS	NM_000516.7	8, 9	196-218, 221-239
HRAS	NM_005343.4	2, 3, 4	6-33, 45-86, 107-139
IDH1	NM_005896.4	4	101-138
IDH2	NM_002168.4	4	162-178
KIT†	NM_000222.3	9, 10, 11, 13, 14, 15, 17	488-513, 517-549, 550-588, 629-663, 665-687, 715-727, 788-826
KRAS†	NM_004985.5	2, 3, 4, 5	6-37, 38-65, 113-150, 151-175
MAP2K1	NM_002755.4	2, 3, 4	44-81, 98-135, 191-226
MET*†	NM_000245.4	2, 9, 11, 13, 14, 15, 16, 19, 20, 21
+5′ & 3′ Flanking regions of exon 14	152-191, 345-383, 751-754, 844-879, 969-980, 982-994, 1009-1027, 1029-1052, 1106-1131, 1234-1274, 1289-1328, 1331-1369
MTOR	NM_004958.4	30, 39, 40, 43, 44, 47, 53	1449-1498, 1789-1811, 1872-1904, 1971-1996, 2012-2040, 2187-2220, 2394-2433
MYD88	NM_002468.5	3, 4, 5	185-211, 216-234, 247-255
NRAS	NM_002524.5	2, 3, 4	1-21, 43-68, 113-149
NTRK1	NM_002529.4	14, 15	554-597, 645-674
NTRK3	NM_001012338.3	16, 17
PDGFRA	NM_006206.6	12, 14, 15, 18	552-584, 644-667, 669-701, 835-854
PIK3CA†	NM_006218.4	2, 3, 5, 6, 8, 10, 12, 14, 19, 21	23-57, 78-108, 119-137, 312-351, 354-381, 418-443, 452-468, 533-554, 585-627, 694-729, 896-924, 1020-1059
POLD1	NM_002691.4	8, 10, 12, 13, 17	283-323, 380-414, 462-498, 499-549, 670-716
POLE	NM_006231.4	9, 11, 12, 13, 14, 19, 31, 32, 34, 41	268-303, 341-368, 370-408, 410-453, 454-491, 689-724, 1272-1315, 1346-1383, 1434-1460, 1852-1889
PTEN	NM_000314.8	1, 2, 3, 4, 5, 6, 7, 8, 9	1-26, 28-46, 56-69, 79-84, 86-106, 123-158, 165-181, 213-234, 283-299, 313-342, 343-353
RET	NM_020975.6	3, 6, 10, 11, 13, 14, 15, 16	114-120, 356-387, 610-626, 628-634, 665-706, 763-797, 799-817, 831-869, 876-910, 911-925
ROS1	NM_02944.3	37, 38, 40	1981-2001, 2003-2036, 2082-2122
SMAD4	NM_005359.6	2, 3, 6, 9, 10, 11, 12	18-58, 110-139, 224-254, 336-374, 385-424, 443-478, 484-511, 526-553
STK11	NM_000455.5	1, 4, 5, 6, 7, 8	27-57, 162-189, 206-235, 269-287, 291-306, 318-359
TP53	NM_000546.6	2, 3, 4, 5, 6, 7, 8, 9, 10, 11	1-18, 27-32, 53-94, 108-125, 138-180, 188-222, 225-251, 262-302, 308-331, 332-343, 356-366

*including selected DNA variants which have been associated with MET exon 14 skipping
†Validated for assessment of copy number gain. Not assessable in samples with <20% tumour.

Fusions (MGP-4RNA)

Fusion – A hybrid of two separate genes (caused by translocations, interstitial deletions, or chromosomal inversions)

*including selected DNA variants which have been associated with MET exon 14 skipping
^†Validated for assessment of copy number gain. Not assessable in samples with <20% tumour. 

Internal Gene Rearrangements

Rearrangements within a gene resulting in an abnormal transcript

Gene	Alias	Description
EGFR‡	EGFRvIII EGFR-EGFR.E1E8	Rearrangement resulting in the loss of exons 2 through 7
MET‡	MET Exon14 Skipping MET-MET.M13M15	Rearrangement resulting in the loss of exon 14

^‡Validated for detection of inter- or intra-genic rearrangement events

Gene	RefSeq Transcript	Exons	Codons
DPYD	NM_000110.3	Intron 10-11, 11, 13, 14, Intron 14-15, 22	386-427, 530-569, 630-635, 932-969
ENOSF1	NM_202758.5	Intron 10-11	–
G6PD	NM_000402.4	4, 5, 7	92-119, 149-182, 246-261
TPMT	NM_000367.4	4, 6, Intron 8-9	79-82, 146-164
UGT1A1	NM_000463.2	Intron 0-1, 1	65-106

 

MGP-5

Our Homologous Recombination Deficiency Panel

This is our latest Multi-Gene Panel (MGP), offering comprehensive sequencing of the full coding region of 15 key genes (see below) involved in the homologous recombination repair pathway. This is intended to help guide the use of therapies such as PARPi inhibitors in certain tumour types (e.g. Breast, Prostate, Ovarian, Pancreatic)  which may exhibit homologous recombination deficiencies.

Please note: 1) This test does not provide a measure of genomic instability.

SNVs & Small Indels

SNV – A single nucleotide variant; Small Indel – An Insertion, deletion or substitution of between 1 and 50 nucleotides

Gene	RefSeq Transcript
ATM	NM_000051.4
BARD1	NM_000465.4
BRCA1	NM_007294.4
BRCA2	NM_000059.4
BRIP1	NM_032043.3
CDK12	NM_016507.4
CHEK2	NM_007194.4
FANCD2	NM_001018115.3
MRE11	NM_005591.4
NBN	NM_002485.5
PALB2	NM_024675.4
PPP2R2A	NM_002717.4
RAD51B	NM_133510.4
RAD54L	NM_003579.4
TP53	NM_000546.6